Department of Pediatrics, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 310000, Hangzhou, Zhejiang, China.
Department of Pathology, Ministry of scientific research and discipline construction, Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, 314001, Jiaxing, Zhejiang, China.
Diagn Pathol. 2023 Mar 30;18(1):41. doi: 10.1186/s13000-023-01330-y.
Epithelioid and spindle rhabdomyosarcoma (ES-RMS) with TFCP2 rearrangement is a recently discovered rare variant of rhabdomyosarcoma composed of epithelioid and spindle cells, because it shows extraordinarily adverse prognosis and is easily misdiagnosed as other epithelioid or spindle cell tumors.
A rare case of ES-RMS with TFCP2 rearrangement was presented and English literatures in Pubmed online up to 01 July 2022 were gathered by two authors for a systematic review according to the inclusion and exclusion criteria.
CASE PRESENTATION/RESULTS: We report a case of ES-RMS in an early 30s-years-old female, the neoplastic cells are remarkably immunoreactive with CK(AE1/AE3), and partially with ALK protein. Unexpectedly, the tumor shows TFCP2 rearrangement with coexistence of increased copy numbers of EWSR1 and ROS1 gene and MET gene mutation. Besides, Next-generation sequencing for genetic mutational profiling revealed frequent MET exon14 mutations in chromosome 7, most of which are C > T nonsynonymous SNV, and exon42 of ROS1 in chromosome 6 showed frequent G > T mutation up to 57.54%. In addition, neither MyoD1 mutation nor gene fusions were detected. Moreover, the patient shows high tumor mutational burden (TMB) up to 14.11 counts/Mb. Finally, as many cases of ES-RMS including our case had local progression or metastasis, we find, similar to epithelioid rhabdomyosarcoma (median survival time is 10 month), ES-RMS shows a more aggressive behavior and adverse prognosis (median survival time is 17 month) than spindle cell/sclerosing rhabdomyosarcoma (median survival time is 65 month) according previous studies.
ES-RMS with TFCP2 rearrangement is a rare malignant tumor and easily confused with other epithelioid or spindle cell tumors, it may harbor additional gene alteration in addition to TFCP2 rearrangement, such as MET mutation, increased copy numbers of EWSR1 and ROS1 gene, high TMB. Most importantly, it may show very poor outcome with extensive metastasis.
具有 TFCP2 重排的上皮样和梭形横纹肌肉瘤（ES-RMS）是一种最近发现的罕见横纹肌肉瘤变体，由上皮样和梭形细胞组成，因为它表现出异常不良的预后，并且容易误诊为其他上皮样或梭形细胞瘤。
呈现了一例具有 TFCP2 重排的 ES-RMS 罕见病例，并根据纳入和排除标准，由两位作者通过在线 Pubmed 收集截至 2022 年 7 月 1 日的英语文献进行系统综述。
病例介绍/结果：我们报告了一例 30 岁出头的女性 ES-RMS 病例，肿瘤细胞显著免疫反应性 CK(AE1/AE3)，部分反应性 ALK 蛋白。出乎意料的是，肿瘤显示 TFCP2 重排，同时 EWSR1 和 ROS1 基因的拷贝数增加，以及 MET 基因突变。此外，下一代测序进行的遗传突变分析显示，7 号染色体上的 MET 外显子 14 频繁突变，大多数是 C>T 非同义 SNV，6 号染色体上的 ROS1 外显子 42 频繁 G>T 突变，高达 57.54%。此外，没有检测到 MyoD1 突变或基因融合。此外，患者的肿瘤突变负担（TMB）很高，达到 14.11 个计数/Mb。最后，由于包括我们的病例在内的许多 ES-RMS 病例都有局部进展或转移，我们发现，与上皮样横纹肌肉瘤（中位生存时间为 10 个月）相似，ES-RMS 表现出更具侵袭性的行为和不良预后（中位生存时间为 17 个月），与梭形细胞/硬化性横纹肌肉瘤（中位生存时间为 65 个月）相比，根据以往的研究。
具有 TFCP2 重排的 ES-RMS 是一种罕见的恶性肿瘤，容易与其他上皮样或梭形细胞瘤混淆，它可能除了 TFCP2 重排之外还存在其他基因改变，如 MET 突变、EWSR1 和 ROS1 基因的拷贝数增加、高 TMB。最重要的是，它可能表现出广泛转移的非常不良的结局。
